||Saikosaponin A has a variety of pharmacological benefits, including antiepileptic, anti-osteoporosis, antioxidant, anti-inﬂammatory, immunomodulatory, and anti-bacterial activities. It extends to alcohol self-administration the capacity to suppress morphine and cocaine self-administration in rats, and can effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of p38 MAPK and NF-κB signaling pathways in spinal cord. It can inhibit NMDA receptor current and persistent sodium current, and inhibit the TNF-α level, the IL-1β production, and cysteine-aspartic acid protease (caspase)-1 activity.
||COX | NOS | TNF-α | IL Receptor | NF-kB | p65 | p38MAPK | JNK | ERK | GABA Receptor | Caspase | Potassium Channel | IkB | IKK|
|Int Immunopharmacol. 2015 Mar;25(1):49-54. |
|Saikosaponin a inhibits RANKL-induced osteoclastogenesis by suppressing NF-κB and MAPK pathways.[Pubmed: 25617149]|
|Inflammatory cytokines play an important role in osteoclastogenesis. Saikosaponin A (SSa) possesses anti-inflammatory activity. However, the role of SSa in osteoporosis is still unclear.
Therefore, the objective of this study was to investigate the effects of SSa on receptor activator of the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and signaling pathway by in vitro assay.
METHODS AND RESULTS:
In mouse bone marrow monocytes (BMMs), SSa suppressed RANKL plus macrophage colony-stimulating factor (M-CSF)-induced osteoclast differentiation in a dose-dependent manner. Moreover, SSa decreased osteoclastogenesis-related marker proteins expression, including NFATc1, c-fos and cathepsin K. At molecular levels, SSa inhibited RANKL-induced IκBα phosphorylation, p65 phosphorylation and NF-κB luciferase activity in RAW264.7 cells. And SSa also suppressed RANKL-induced p-38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation.
Taken together, these findings suggest that SSa suppresses osteoclastogenesis through inhibiting RANKL-induced p-38, ERK, JNK and NF-κB activation. SSa is a novel agent in the treatment of osteoclast-related diseases, such as osteoporosis.
|Evid Based Complement Alternat Med. 2013;2013:413092. |
|Saikosaponin a Enhances Transient Inactivating Potassium Current in Rat Hippocampal CA1 Neurons.[Pubmed: 23554830 ]|
|Saikosaponin A (SSa), a main constituent of the Chinese herb Bupleurum chinense DC., has been demonstrated to have antiepileptic activity. Recent studies have shown that SSa could inhibit NMDA receptor current and persistent sodium current. However, the effects of SSa on potassium (K(+)) currents remain unclear.
In this study, we tested the effect of SSa on 4AP-induced epileptiform discharges and K(+) currents in CA1 neurons of rat hippocampal slices.|
METHODS AND RESULTS:
We found that SSa significantly inhibited epileptiform discharges frequency and duration in hippocampal CA1 neurons in the 4AP seizure model in a dose-dependent manner with an IC 50 of 0.7 μ M. SSa effectively increased the amplitude of I Total and I A , significantly negative-shifted the activation curve, and positive-shifted steady-state curve of I A . However, SSa induced no significant changes in the amplitude and activation curve of I K . In addition, SSa significantly increased the amplitude of 4AP-sensitive K(+) current, while there was no significant change in the amplitude of TEA-sensitive K(+) current.
Together, our data indicate that SSa inhibits epileptiform discharges induced by 4AP in a dose-dependent manner and that SSa exerts selectively enhancing effects on I A . These increases in I A may contribute to the anticonvulsant mechanisms of SSa.
|Neurosci Lett. 2016 May 16;621:62-67. |
|Reducing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on alcohol self-administration in rats: Possible involvement of the GABAB receptor.[Pubmed: 27080427 ]|
|Recent studies demonstrated that treatment with Saikosaponin A (SSA) - an active ingredient of the medicinal herb, Bupleurum falcatum L. - selectively suppressed, likely via a GABAB receptor-mediated mechanism, intravenous self-administration of morphine and cocaine in rats [Yoon et al., 2012; 2013].
The present study was designed to investigate whether the capacity of SSA to suppress morphine and cocaine self-administration extends to oral alcohol self-administration.
METHODS AND RESULTS:
To this end, selectively bred Sardinian alcohol-preferring (sP) rats were trained to lever-respond on a Fixed Ratio (FR) 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested under the FR4 (measure of alcohol reinforcing properties) and Progressive Ratio (PR; measure of alcohol motivational properties) schedules of reinforcement. The possible involvement of the GABAB receptor system was investigated testing the effect of (a) pretreatment with the GABAB receptor antagonist, SCH50911, and (b) combined treatment with the positive allosteric modulator of the GABAB receptor, GS39783. Treatment with SSA (0, 0.25, 0.5, and 1mg/kg, i.p.) markedly reduced lever-responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol (defined as the lowest response requirement not achieved in the PR experiment). Pretreatment with 2mg/kg SCH50911 (i.p.) resulted in a partial blockade of the reducing effect of 0.5mg/kg SSA on lever-responding for alcohol and amount of self-administered alcohol. Combination of per se ineffective doses of GS39783 (5mg/kg, i.g.) and SSA (0.1mg/kg, i.p.) reduced lever-responding for alcohol and amount of self-administered alcohol.
These results (a) extend to alcohol self-administration the capacity of SSA to suppress morphine and cocaine self-administration in rats and (b) suggest that the GABAB receptor system is likely part of the neural substrate underlying the reducing effect of SSA on alcohol self-administration.
|Am. J. Chinese Med., 2012, 38(1):99-111. |
|Curcumin and Saikosaponin A Inhibit Chemical-Induced Liver Inflammation and Fibrosis in Rats[Pubmed: 20128048]|
|Curcumin and Saikosaponin A as antioxidants improve antioxidant status. This study investigated the anti-inflammatory and antifibrotic actions of curcumin and Saikosaponin A on CCl(4)-induced liver damage.
METHODS AND RESULTS:
Sprague-Dawley rats were randomly divided into control, CCl(4), CCl(4)+ curcumin (0.005%; CU), CCl(4) + Saikosaponin A (0.004%; SS), and CCl(4) + curcumin + Saikosaponin A (0.005% + 0.004%; CU + SS) groups. Carbon tetrachloride (40% in olive oil) at a dose of 0.75 ml/kg was injected intraperitoneally once a week. Curcumin and Saikosaponin A were supplemented alone or in combination with diet 1 week before CCl(4) injection for 8 weeks. After 8-week supplementation, histopathological results showed hepatic collagen deposition was significantly reduced in the CU and SS groups, and activated nuclear factor-kappa B expression induced by CCl(4) in the liver was significantly inhibited by curcumin and/or Saikosaponin A. Hepatic proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were significantly inhibited, and anti-inflammatory cytokine interleukin-10 was significantly increased by supplementation with curcumin and/or Saikosaponin A. Additionally, curcumin and/or Saikosaponin A significantly reduced the increased levels of hepatic transforming growth factor-beta1 and hydroxyproline after CCl(4) treatment.
Therefore, supplementation with curcumin and/or Saikosaponin A suppress inflammation and fibrogenesis in rats with CCl(4)-induced liver injury. However, the combination has no additive effects on anti-inflammation and antifibrosis.